Apheresis and hemodialysis methods are used to treat a variety of disease states which manifest themselves as a detrimental and potentially toxic increase of an innate or newly-presented component of the circulation system. Hemodialysis, for example, is used for treating patients suffering from renal failure; it involves the use of an artificial kidney to clear urea, metabolic waste products, toxins, and excess fluid from the blood before the blood is returned to the patient. Therapeutic apheresis is a procedure wherein whole blood is withdrawn from a patient, separated into two or more fractions, and at least one of the separated blood fractions is re-transfused into the patient, while the other fraction containing an unwanted or detrimental blood component is removed (discarded). The most common type of apheresis procedure is known as “plasmapheresis”. In plasmapheresis, a quantity of liquid plasma is separated from a cell concentrate comprising the remaining liquid and cellular constituents of the blood and such cell concentrate is, thereafter, re-transfused into the donor. This process may remove whole cells or a specific population of cells. Other types of apheresis procedures include “leukapheresis” (wherein leukocytes are separated from whole blood) and “thrombocytapheresis” (wherein platelets are separated from whole blood). Apheresis procedures are also commonly carried out to harvest commercially usable blood components.
A number of devices and filter appliances directed at separation of various blood components have been developed and are commercially available for performing hemodialysis. For example, Fresenius Medical Care (Waltham, Mass.) manufactures a number of dialysis machines and membrane dialyzers (such as the Optiflux® Advanced Fresenius Polysulfone® and Hemoflow™ dialyzers) for separating waste components, such as urea, from a patient's blood using an extracorporeal circuit. Fresenius also manufactures and sells devices for therapeutic apheresis directed at removal of low density lipoprotein (LDL), e.g., to treat hypercholesteremia and for immunoadsorption, e.g., to remove autoantibodies from patients suffering from an autoimmune disorder (see, Prosorba®, Globaffin®, Immunosorba® dialysis products). These devices are used to substantially deplete the targeted molecules, for example immunoglobulins, from a patient's plasma using an extracorporeal circuit.
Apheresis devices reflect a variety of configurations and designs. U.S. Pat. No. 6,497,675 to Davankov describes an apheresis device for removal of low molecular weight toxins from a subject's blood by use of a hollow fiber membrane permitting passage of low molecular weight components of blood, which are then contacted with a particulate adsorbent material before remixing with the larger molecular weight components of the blood prior to return of the treated blood to the subject. U.S. Pat. No. 6,039,946 to Strahilevitz describes an extracorporeal affinity adsorption device for removing at least two chemical species from a body fluid of a patient. The system contains a complex circuit for on-line regeneration of a chelant. Such devices enhance the properties or cost-effectiveness of apheresis without altering the basic purpose of the apheresis techniques, which is the depletion or removal of a detrimental component from whole blood or other body fluid of a patient.
There has also been variegation of the targets addressed by apheresis devices as new classes of affinity materials have become available and new target molecules associated with disease states have been identified. For example, US Pat. Publication. 2007/0026029 (Mattner et al.) describes an apheresis device having a solid support containing a receptor for the capture of amyloid-β-precursor-protein from a subject's blood, for treating or preventing Alzheimer's disease. U.S. Pat. No. 4,430,229 (Yamawaki et al.) describes purine- or pyrimidine-based adsorbers for autoantibodies and immune complexes associated with collagen disorders such as systemic lupus erythematosus. WO 2006/017763 (Ellson and Mutz) describes removal of targeted biomolecules from a body fluid of a subject by contacting the fluid with a matrix of molecular imprint materials; U.S. Pat. No. 4,685,900 (Honard) describes removal of targeted biomolecules from a subject by contacting a body fluid with a specific biological ligand immobilized on a biocompatible polymer support (e.g., immobilized insulin molecules targeting anti-insulin autoantibodies in a diabetic); and U.S. Pat. No. 6,866,846 (Heinrich et al.) describes the preparation of patient-specific immunoadsorbers derived from immune complexes isolated from the patient.
All of the techniques/devices described above are designed for one primary purpose: to relieve or minimize the detrimental effect that a component of whole blood is exacting upon the patient by utilizing apheretic techniques to remove a significant proportion of the blood component permanently from the patient's circulation. In order to remove a physiologically beneficial amount of the component of interest, these techniques require the processing of large volumes of blood and the return of the depleted plasma to the patient. None of these methods or devices described above contemplate the isolation and modification of a targeted blood component, nor the return of the modified blood component to the patient, all within an extracorporeal closed-circuit apparatus.